Chemotherapy using an anticancer agent is known as an example of anticancer therapies. Pathological conditions of cancer patients, however, differ one from another depending on the type of the cancer, the area affected by the cancer, the stage of progression, or other factor. The versatile pathological conditions and difference in responsiveness among cancer patients mean that some patients have to be treated with a chemotherapy using an anticancer agent which is ineffective to them, while the others receive benefits from an effective chemotherapy using an anticancer agent. Continuing administration of an anticancer agent that is not effective to a patient may only increase an adverse effect due to a side-effect, which may impose unwanted suffering to the patient.
In view of the above, there is a demand for a technique of predicting, with high probability, the effectiveness of an anticancer agent for patients at an early stage of administration of the agent.
As a method for predicting the chemosensitivity of patients to an anticancer agent, Japanese Unexamined Patent Publication No. 2003-199585 (D1), for instance, discloses a method for assessing the chemosensitivity of specimen cells to an anticancer agent, wherein gene polymorphisms of BCRP contained in the specimen cells are identified based on an idea that a difference in chemosensitivity is due to the gene polymorphisms.
BCRP is an example of ABC transporters, and is known to be associated with resistance to an anticancer agent. Also, it is known that a difference in BCRP expression among the individuals is caused by single nucleotide polymorphisms (SNPs). In view of this, the chemosensitivity assessing method disclosed in D1 comprises the steps of examining the DNA sequence of cancer cells obtained from a patient; identifying a polymorphism of gene encoding BCRP; and assessing the chemosensitivity of the cancer cells to the anticancer agent or the degree of a side-effect of the anticancer agent.
Also, Japanese Unexamined Patent Publication No. 2003-304884 (D2) discloses a method comprising specifying a marker gene having compatibility to an anticancer agent with reference to the chemosensitivity of a cultured cancer cell line, and a gene expression profile of the cancer cell line in an intact state, and measuring an expression level of the corresponding to the specified marker gene in the cancer cell line of the specimen to predict compatibility of the specimen to the anticancer agent based on the obtained the expression value.
In the method disclosed in D2, if the gene group in the cancer cells of the specimen having a high relative expression amount has a high matching rate to the marker gene group having a high correlation to a certain anticancer agent, it is predicted that the specimen has compatibility to the anticancer agent. If, on the other hand, the gene group in the cancer cells in the specimen having a high relative expression amount does not show any matching to the marker gene group having a high correlation to the anticancer agent, it is predicted that the specimen does not have compatibility to the anticancer agent.
Even if the anticancer agent which is assessed to have compatibility by the above method is used for chemotherapy, it is known that the actual effectiveness of the chemotherapy is about 80%. The effectiveness of 80% is not a high rate for selecting a chemotherapy using the anticancer agent. Accordingly, an effectiveness indicator with higher probability is required for undergoing the chemotherapy in clinical facility.
There is known that p53, which is an oncosuppressor protein encoded by the p53 gene, or a retinobiastoma (RB) protein is associated with cell cycle control. In view of this, in recent years, a study has progressed concerning a relation between cancer and cell cycle related protein.
WO2004-076686 (D3) implies that a drug resistance test and prognosis are enabled by measuring at least two kinds of cell cycle related proteins and obtaining a profile of the cell cycle related proteins. D3, however, has no disclosure about a specific method or effect of the method.